Statins May Boost Efficacy of Rho-Kinase Inhibitors in Pulmonary Arterial Hypertension

Statins, the cholesterol lowering drugs, may improve the beneficial effects of Rho-kinase inhibitors in pulmonary arterial hypertension (PAH), according to the results of an animal study performed by researchers at the Medical University of Lodz, in Poland.

The study, titled “Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension,” published in the journal Archives of Medical Science, suggests that combining both these drugs reduces PAH symptoms more effectively than Rho-inhibitors alone.

It is thought that Rho-kinases play an important role in PAH pathology by participating in the contraction and proliferation of the muscle cells that line the pulmonary arteries. In recent animal studies, as well as in small clinical trials, inhibition of Rho-kinases with fasudil (HA-1077) has shown beneficial effects in PAH symptoms, including improvement of hemodynamic parameters and pulmonary vascular remodeling, as well as amelioration of endothelial dysfunction.

Although statins are known for their role in decreasing serum cholesterol, they exert a variety of effects that include the restoration of endothelial function and the inhibition of vascular inflammation and oxidative stress. A number of studies have addressed the effects of statins in PAH, but the results remain controversial.

Now, researchers assessed whether combining fasudil with the statin rosuvastatin could improve the outcomes of a pulmonary hypertension (PH) rat model. Thirty-two male rats induced with monocrotaline (MCT) to develop PH were assigned to receive either a combination of fasudil and rosuvastatin, or fasudil alone.

Results revealed that the drug combination was able to reverse the MCT-induced increase in right ventricle pressure and reduced right ventricular hypertrophy more effectively than fasudil alone. Interestingly, the simultaneous administration of fasudil and rosuvastatin induced a greater decrease in RhoA kinase activity in lung tissues isolated from the MCT-induced rats compared to fasudil alone.

Such results are consistent with those observed in a very recent study, where the synergy of fasudil and another statin called pitavastatin was observed in a rabbit model of subarachnoid hemorrhage.

The researchers believe that this synergy is clinically relevant, because it offers the possibility of reducing the dose of fasudil, easing the drug’s side effects, which include an increased risk of systemic vasodilation. But further studies are required, they said, to evaluate both the precise mechanism through with the drugs interact and their effectiveness in patients with PAH.